This application seeks to investigate relationships between changes in the biophysical environment of water and focal cerebral ischemia using Nuclear Magnetic Resonance (NMR). The degree and duration of reductions in regional cerebral blood flow (rCBF) and a well defined biological end- point of tissue damage will be characterized in terms of NMR-measurable parameters in a rat model of stroke (middle cerebral artery occlusion). The 1H NMR-measurable parameters of water (T1, T2, p and ADCw), are sensitive to changes in the biophysical environment of water (i.e., rotation, translation, concentration). NMR imaging will be used to characterize the spatial distribution and temporal evolution of changes in the biophysical environment of water. Additionally, a mechanism for the ischemia-induced reduction in the apparent diffusion coefficient of water (ADCw) will be [investigated]. It is proposed that an understanding of changes in the biophysical environment of water will lead to a better understanding of the mechanisms involved in ischemic brain damage. This approach may eventually provide a means for the non- invasive determination of the degree, severity, and status of stroke induced brain damage in humans.